Renal Graft Survival Research Articles

Outcomes of Male Patients with Alport Syndrome Undergoing Renal Replacement Therapy

Patients with the hereditary disease Alport syndrome commonly require renal replacement therapy (RRT) in the second or third decade of life. This study compared age at onset of RRT, renal allograft, and patient survival in men with Alport syndrome receiving various forms of RRT (peritoneal dialysis, hemodialysis, or transplantation) with those of men with other renal diseases. Patients with Alport syndrome receiving RRT identified from 14 registries in Europe were matched to patients with other renal diseases. A linear spline model was used to detect changes in the age at start of RRT over time. Kaplan-Meier method and Cox regression analysis were used to examine patient and graft survival. Age at start of RRT among patients with Alport syndrome remained stable during the 1990s but increased by 6 years between 2000-2004 and 2005-2009. Survival of patients with Alport syndrome requiring dialysis or transplantation did not change between 1990 and 2009. However, patients with Alport syndrome had better renal graft and patient survival than matched controls. Numbers of living-donor transplantations were lower in patients with Alport syndrome than in matched controls. These data suggest that kidney failure in patients with Alport syndrome is now being delayed compared with previous decades. These patients appear to have superior patient survival while undergoing dialysis and superior patient and graft survival after deceased-donor kidney transplantation compared with patients receiving RRT because of other causes of kidney failure.

Inosine Monophosphate Dehydrogenase Polymorphisms and Renal Allograft Outcome

Interindividual variation in inosine monophosphate dehydrogenase (IMPDH) enzyme activity and adverse effects caused by mycophenolate mofetil (MMF) inhibition may be genetically determined, and if so, transplant recipients should receive personalized dosing regimens of MMF, which would maximize efficacy and minimize toxicity. Some studies have demonstrated a relationship between the single nucleotide polymorphism and the risk of acute rejection with IMPDH I variants rs2278293 and rs2278294 and IMPDH II variant rs11706052, whereas others have failed to exhibit an effect. The aim of this work was to investigate the influence of these polymorphisms on acute rejection rates, graft survival and function, and MMF doses in a large cohort of patients. A random sample of 1040 recipients from the Collaborative Transplant Study DNA bank was genotyped for the variants IMPDH I rs2278293 and rs2278294 and IMPDH II rs11706052. The presence of the T (rs2278293) and G alleles (rs2278294) in the IMPDH I variants and carriage of the G allele (rs11706052) in the IMPDH II variant did not increase the risk of rejection or affect graft function by 1 year after transplantation. There was no association with MMF dose tolerated at 1 year. Furthermore, these polymorphisms did not impact graft or patient survival at 5 years. This study represents the largest cohort of patients with the longest follow-up to date and does not support previous evidence for an association between these IMPDH variants and renal allograft rejection and graft survival.

Aggressive lung donor management increases graft procurement without increasing renal graft loss after transplantation

To determine the impact of an aggressive protocol on the rate of lung grafts available for transplant. We analyzed the impact of this management on kidney graft survival after kidney transplantation. A cohort study. Lung donors and kidney recipients from 2009 and 2010 were considered the prospective cohort with 2003-2008 as the historical control period. The number of lungs available for transplantation was the main outcome measures. For recipients, kidney graft survival was the main outcome measure. We quadrupled the number of lung donors in the period 2009-2010 compared with the historical control. Management in the prospective cohort included higher use of positive end-expiratory pressure (PEEP) (p < 0.0001), increased use of hormonal resuscitation therapy (HRT) (p < 0.0001), and lower level of central venous pressure (p < 0.05) than historical control. The probability of renal graft survival at one yr after transplant was 88.6% (CI 95%: 74.8-95.1) in historical control and 94.7% (CI 95%: 81-98.7%) in the prospective cohort (p = 0.226). Aggressive management strategy in potential lung donors, which includes ventilator recruitment maneuvers, PEEP ≥ 8 cm H(2)O, the use of HRT, and restrictive fluid balance increases the rate of lung grafts available for transplantation without adverse effect on kidney graft survival.

Biomarkers for long-term survival of renal graft: recent progress

How to maintain a good long-term graft function is currently the most prominent problem in renal transplantation.Due to inefficiency of the existing diagnostic tools,extensive studies have been made to search for novel biomarkers and have made rapid progression.Here we aimed to make a brief review of important biomarkers that have been shown relevant to the long-term outcome of renal graft.

Hyperuricemia at 1 Year After Renal Transplantation, Its Prevalence, Associated Factors, and Graft Survival

The present study investigated the prevalence and predictors for the development of hyperuricemia within 1 year after transplantation and their associations with genetic polymorphisms and graft outcome in patients taking tacrolimus and mycophenolate mofetil. One hundred twenty-one renal allograft recipients transplanted between January 2001 and March 2009 were studied. Patients with serum uric acid concentrations above 7.0 mg/dL within 1 year after transplantation were defined as having hyperuricemia, and all were treated with allopurinol. Genetic polymorphisms of nitric oxide synthase, angiotensin-converting enzyme, methylenetetrahydrofolate reductase, and 3 uric acid transporters were examined. At 1 year after transplantation, 46 (38%) recipients developed hyperuricemia. Male gender, higher body mass index, long-term pretransplantation dialysis, and hypertension were associated with the development of hyperuricemia. The estimated glomerular filtration rate (eGFR) at 1 year after transplantation was lower in the patients with hyperuricemia than in those without. There were no differences in graft survival between the two groups. The pharmacokinetics of tacrolimus and mycophenolic acid and 6 polymorphisms were not associated with hyperuricemia. In the multivariate analysis, male gender, long-term pretransplantation dialysis (>36 months), and eGFR (<60 mL/min) were independently associated with the development of hyperuricemia. The incidence of hyperuricemia in our cohort was 38%. Male gender and long-term pretransplantation dialysis were predictors for the development of hyperuricemia. The eGFR was lower in patients with hyperuricemia, but graft survival did not differ between the patients with hyperuricemia treated with alloprinol and those without hyperuricemia. We could not define the significance of the pharmacokinetics of immunosuppressants and genetic risk factors for hyperuricemia.

Should Functioning AV Fistulas be Ligated after Renal Transplantation?

There is limited literature available to guide physicians on a course of action when they are approached by renal transplant recipients regarding the status of their vascular accesses. However, this is a frequent topic of discussion with these patients and there should be guidelines available to assist in the decision of whether to maintain or ligate an arteriovenous fistula (AVF) in a successful renal transplant patient. This review intends to present some of the literature, as well as to establish guidelines for management. The medical literature was reviewed and anecdotal information from our clinical experience was collected. Taking into account 10-year adjusted renal transplant graft survival rates, and the relative paucity of donors, it is possible that a successfully transplanted patient will have to return to dialysis at some point. After review of the literature, the impact of AVF ligation on the transplant patient's cardiac morphology and function is not clear. Patient and graft survival do not appear to be impacted by persistent AVFs. Emergent closure of the AVF might be required in cases of severe venous hypertension, risk of rupture from pseudoaneurysm, significant high output cardiac failure or ischemic hand. We recommend that following successful renal transplantation, functioning AVFs should almost never be ligated. Many patients require return to dialysis and the physiologic impact of the patent AVF on these patients does not strongly advocate routine ligation following transplant.

Alargamiento de la vena renal derecha en 120 trasplantes consecutivos. Análisis comparativo

ObjectivesShorter length of the right renal vein (RRV) may represent an additional difficulty for transplant. This paper has aimed to present our experience with RRV elongation in the kidney from a cadaveric donor and to compare the results with the rest of kidneys transplanted in the same period of time. Material and methodsWe performed 377 kidneys transplants within the last 11 years. Of these, in 120, the RRV was elongated with the vena cava. The surgical technique is described and the results compared with the remaining transplants of the series. Renal function, graft survival and complications were assessed at 1, 3 and 12 months. Data were obtained retrospectively from the database of the Urology Department and Hospital medical records. ResultsIn the 377 transplants, there were 4 (1%) venous thrombosis, 2 (1.6%) of which concerned kidneys with elongation of the RRV and 2 (0.7%) in the rest of transplanted kidneys. There was no difference in postoperative bleeding, 11 (9.1%) occurred in kidneys with elongated RRV and 22 (8.5%) in the remaining kidney. In no case was the bleeding related to the elongated segment. Graft survival and renal function were similar for both groups. ConclusionsElongation of the RRV with the vena cava is a feasible, fast, and effective procedure that does not increase morbidity or affect renal function or graft viability. It facilitates vascular anastomosis and places the kidney in a less forced position, shortens the warm ischemia time and avoids the risk of kinking of the renal artery because it is equal to the length of the vein artery.

PP106. Risk of long term renal graft loss after pregnancy in renal transplant recipients immunosuppressed with calcineurin inhibitors

IntroductionIntron long-term graft function are uncertain. Although there have been a large number of successful pregnancies in renal graft recipients, the effects of pregnancy and type of immunosuppressant drugs. ObjectivesTo analyze (1) the impact of pregnancy on the long term renal function and graft survival of kidney transplant recipients (KTx), and (2) the impact og the pregnancy in (KTx) immunosupressed with calcineurin inhibitors (CNI). MethodsRetrospective analysis of two cohorts: one (PG) formed by all the KTx recipients from our institution that became pregnant between 1973 and 2004, and the other one (NPG) formed by, when possible, up two KTx patients of similar demographic and clinical characteristics: patient age, donor source, donor age, interval between KTx and pregnancy (or a matched interval for NPG), baseline renal function before pregnancy, hypertension, proteinuria >1g, and CNI-based immunosuppression. but without pregnancies. Particular attention has been paid to long-term (5 and 10years) renal function and graft survival. Males were selected to complete NPG if no matched women were available. Statistical analysisAssessment of baseline homogeneity between the two cohorts was performed by appropriate analysis. Time of survival of kidney was estimated by means Kaplan–Meier method and the Cox proportional hazard model was used to perform adjusted analysis. ResultsFifty five pregnancies in 43 patients (PG) and 68 paired controls (NPG) were included in the study. The basal and functional characteristics of PG before pregnancy and NPG were not statistical and clinical significantly different. In a univariate Cox regression analysis, 10 years graft survival after pregnancy/study entry was significantly better in CG (79.9%) than PG (60.9%) (P=0.02). Multivariate analysis of graft survival showed an increased risk of long-term graft loss in pregnant women that had been treated with CNI as immunosuppressant drug compared with NP KTx that received CNIs (HR: 2.4, 95% CI, 1.17–5.00; P=0.02). In a stratified analysis, evaluating separately the recipients that had received or not CNIs, the risk of graft loss was only increased among recipients that became pregnant post-transplantation treated with CNI compared with recipients that had received CNIs but had not become pregnant (HR: 3.3, 95% CI, 1.42–7.45; P=0.005), but not among recipients that became pregnant post-transplantation and received other immunosuppressant agents (HR: 0.9, 95% CI, 0.24–3.80; P=0.94). ConclusionPregnancy in women receiving baseline immunosuppression with CNI significantly increases the risk of long-term graft loss, non observed in KTx patients treated with CNI that not became pregnant, nor in KTx patients that became pregnant but are treated with other immunosuppressant drugs . At our knowledge, this observation has not been previously reported

Current perspectives to overcome a positive crossmatch in living donor renal transplantation*

Transplantation of a living donor kidney is in general the best treatment option for patients with end-stage renal disease. Two major advantages as compared to transplantation with a deceased donor kidney are the avoidance of waiting time and the superior results in terms of renal function and graft survival. In some patients who are lucky enough to have a person in their neighborhood who are willing to donate a kidney, the transplantation cannot be performed directly because there is ABO blood type incompatibility between donor and recipient, or because of a positive lymphocyte crossmatch, based on the presence of donor-specific antibodies. During recent years, several strategies have been developed to enable transplantation in these cases. A first approach is to use a living donor kidney exchange program, which can result in successful matches in more than half of the crossmatch-positive couples [1]. With the incorporation of kidneys from nondirected, anonymous donors in such an exchange program, domino-paired chains of transplantations can be set up, which end with the transplantation of a living donor kidney to a recipient from the waiting list [2]. However, for a substantial number of recipients, these exchange programs do not result in a successful donor–recipient match. In these cases, desensitization strategies to reduce the titer of ABO blood group antibodies or anti-HLA antibodies can be employed. Desensitization techniques are based on the extracorporeal removal of antibodies, treatment with intravenous immunoglobulins, and on immunosuppressive therapy. Since these procedures carry additional risks for the transplant recipient, desensitization treatment should ideally be reserved for recipients who cannot be served with a donor kidney after several rounds of matching in a (multicenter) exchange program. Unfortunately, kidney exchange programs are not allowed by legislation in every country. In this issue of Transplant International, Morath et al. present the results of living donor kidney transplantation in nine crossmatch-positive patients with peritransplant immunoadsorption (IA) and induction therapy with the anti-CD20 antibody rituximab [3]. Three patients also underwent pretransplant plasmapheresis. In one additional patient with a negative crossmatch but high titers Correspondence L. B. Hilbrands, Department of Nephrology, Radboud University Nijmegen, PO Box 9101, 6500, HB Nijmegen, The Netherlands. E-mail: l.hilbrands@nier.umcn.nl

Long-Term Kidney Allograft Function and Survival in Prednisone-Free Regimens

The optimal maintenance immunosuppressive regimen to improve long-term renal allograft function and graft survival is yet to be determined. This observational study prospectively compared tacrolimus/sirolimus with tacrolimus/mycophenolate mofetil in renal transplant recipients using a prednisone-free regimen with over 8.5 years of follow-up. Patients received methylprednisonlone and anti-IL2 receptor antagonist (Basiliximab) induction and were blindly randomized to either the tacrolimus/mycophenolate mofetil (n=45) or tacrolimus/sirolimus (n=37) groups. Outcome measures included patient and renal allograft survival, incidence of acute rejection, and estimated GFR. The tacrolimus/mycophenolate mofetil group compared with the tacrolimus/sirolimus group had overall better renal allograft survival (91% versus 70%, P=0.02); 13 patients (35.1%) in the tacrolimus/sirolimus group and 8 patients (17.8%) in the tacrolimus/mycophenolate mofetil group experienced biopsy-proven acute cellular rejection (P=0.07). By 3 months post-transplant, estimated GFR was significantly lower in the tacrolimus/sirolimus group compared with the tacrolimus/mycophenolate mofetil group (47.7 versus 59.6 ml/min per 1.73 m(2), P=0.0002), and this trend persisted throughout the follow-up period. Also, the slope of decline in the tacrolimus/sirolimus group was significantly steeper than in the tacrolimus/mycophenolate mofetil group. This study shows that, in a prednisone-free immunosuppressive regimen, long-term renal graft survival and function are significantly worse in the tacrolimus/sirolimus group than the tacrolimus/mycophenolate mofetil group. The synergistic nephrotoxic effect and higher acute rejection rates in the tacrolimus/sirolimus compared with the tacrolimus/mycophenolate mofetil group adversely affect graft survival.

Absolute of CD4+CD25+FOXP3+ Regulatory T-Cell Count Rather Than Its Ratio in Peripheral Blood Is Related to Long-Term Survival of Renal Allografts

CD4+CD25+Foxp3+ regulatory T cells (Tregs) may reflect the immune status of kidney transplant (KTx) recipients. Since individual KTx recipients show different lymphocyte counts, we hypothesized that the Treg absolute count rather than its peripheral ratio was more related to long-term survival. We enrolled 42 patients with more than 5-year KTx survival: 32 patients with stable graft function and 10 suffering chronic rejection (CR group). The stable group was divided into four subgroups according to graft survival time: subgroups A (5–6 years); B (6–7 years); C (7–8 years); and D (>8 years). Healthy volunteers were enrolled as controls. We compared the peripheral ratio and absolute count of CD4+, CD4+CD25+, and CD4+CD25+Foxp3+ Tregs. Treg peripheral ratio was not significantly different among the three groups. However, the Treg absolute count was higher among the stable than the CR group (P < .01). Meanwhile, both Treg ratios and absolute counts were altered with renal graft survival. Treg absolute count in subgroups B and C were not only higher than that in subgroup A (P < .05), but also was significantly higher than that in the CR control group or (P < .05). Interestingly, both the Treg ratio and absolute count in subgroup D were lower than those in subgroups B and C (P < .05). Treg quantitation, which alters with graft survival time, may contribute to long-term acceptance of renal allografts. Compared to Treg peripheral ratio, the absolute count may be a superior index to estimate KTx recipient immune status.

Identification of Risk Factors for Vascular Thrombosis May Reduce Early Renal Graft Loss: A Review of Recent Literature

Renal graft survival has improved over the past years, mainly owing to better immunosuppression. Vascular thrombosis, though rare, therefore accounts for up to one third of early graft loss. We assess current literature on transplantation, identify thrombosis risk factors, and discuss means of avoiding thrombotic events and saving thrombosed grafts. The incidence of arterial thrombosis was reported to 0.2–7.5% and venous thrombosis 0.1–8.2%, with the highest incidence among children and infants, and the lowest in living donor reports. The most significant risk factors for developing thrombosis were donor-age below 6 or above 60 years, or recipient-age below 5-6 years, per- or postoperative hemodynamic instability, peritoneal dialysis, diabetic nephropathy, a history of thrombosis, deceased donor, or >24 hours cold ischemia. Multiple arteries were not a risk factor, and a right kidney graft was most often reported not to be. Given the thrombosed kidney graft is diagnosed in time, salvage is possible by urgent reoperation and thrombectomy. Despite meticulous attentions to reduce thrombotic risk factors, thrombosis cannot be entirely prevented and means to an early detection of this complication is desirable in order to save the kidneys through prompt reoperation. Microdialysis may be a new tool for this.

The Effect of Donor-Recipient Relationship on Long-Term Outcomes of Living Related Donor Renal Transplantation

BackgroundPresensitization to human leukocyte antigen (HLA) tends to decrease renal graft survival. During the pregnancy, fetal blood is frequently exposed to the maternal circulation possibly inducing maternal immunization to paternal HLA inherited by the fetus. In this way, pregnancy may occasionally present a hazard to renal graft survival. In this study, we compared retrospectively graft survivals according to living related donor-recipient pairs. Materials and methodsFrom July 1979 to January 2011, 374 patients underwent living related renal transplantation sharing at least one HLA haplotype with their donor. We compared acute rejection and complication rates as well as long-term graft survival according to the donor-recipient paring: child-to-mother, child-to-father, mother-to-child, father-to-child, and one haplotype-matched siblings. All patients received immunosuppressive therapy, consisting of a calcineurin inhibitor, mycophenolate mofetil, or azathioprine and prednisolone. ResultsTwenty-one cases (5.6%) were child-to-father paring; 28 (7.5%), child-to-mother; 179 (47.9%), one-haplotype-matched siblings; 46 (12.3%), father-to-child; and 100 (26.7%), mother-to-child paring. Child-to-father pairing displayed the best graft survival; child-to-mother (hazard ratio [HR] = 1.709, P = .662) and one-haplotype-matched siblings (HR = 6.589, P = .062) showed no significant difference. Father-to-child pares experienced poorer outcomes than child-to-father pairs (HR = 11.579, P = .017) and mother-to-child, the poorest graft survival (HR 17.188, P = .005). ConclusionPregnancy continues to be a significant source of presensitization in the course of gestation and after parturition. Graft failure can result from an anamnestic reaction subsequent to intrauterine exposure of the mother to HLA of a fetus due to sensitization.

Trends in Maintenance Immunosuppressive Drugs Used in Taiwanese Kidney Transplant Recipients: An Analysis of the National Health Insurance Research Database

Trends in maintenance immunosuppressive drugs used among Taiwanese kidney transplant recipients have not been reported before. We examined the National Health Insurance Research Database to analyze trends in maintenance immunosuppressive drugs used in Taiwanese kidney transplant recipients for the years 2002–2009. The new case number of kidney transplant recipients ranged from 302 to 673 per year. In 2009, 5276 kidney transplant recipients received immunosuppressive therapy. The 5-year renal graft survival rate of kidney transplant recipients was 93%. In 2009, the most common immunosuppressive therapy among Taiwanese kidney transplant recipients was a triple regimen that included tacrolimus, mycophenolate mofetil, and corticosteroid. There was a significant increase in the use of a tacrolimus-based regimen from 35.1%–58.2%, while the use of cyclosporine decreased from 62.2%–24.8% (P < .05). The percentage of calcineurin inhibitor–free regimen increased from 2.7%–17%. Moreover, the use of Rapamune dramatically increased from 8.2%–22.6% in 2002–2004. However, the percentage of kidney transplant recipients using Rapamune maintained 23 ± 1.6% in 2004–2009. The use of mycophenolic acid remained stable at about 74.9 ± 3.2% in 2002–2009. As predicted, the use of Imuran decreased from 6.9%–3.5%. In summary, although calcineurin inhibitors remained the mainstay of immunosuppressive drugs, these findings suggest a general trends toward individualized regimens and the use of calcineurin inhibitor–free and mammalian target of rapamycin inhibitors–based regimens in Taiwanese kidney transplant recipients.

Kidney and liver transplantation in patients with autosomal recessive polycystic kidney disease: a multicentric study

In contrast to the improvement in our understanding of the pathogenesis and presentation of autosomal recessive polycystic kidney disease (ARPKD), data regarding the issue of kidney and liver transplantation in patients with ARPKD remain particularly scarce. Here, we report the results and outcome of renal and/or liver transplantation in a series of patients with ARPKD. Fourteen ARPKD patients (age: 3-25 years) who underwent renal transplantation with or without liver transplantation were retrospectively identified in five French nephrology departments. The patients' medical charts were reviewed and relevant data were collected. The clinical and radiological presentation of the 14 patients was highly variable illustrating the heterogeneity of ARPKD. Six patients underwent kidney and/or liver transplantation in adulthood. First renal graft survival was 92, 78 and 14% at 1, 5 and 10 years after renal transplantation, respectively. Mortality rate was relatively high (3/14; 21%) in these young patients and was directly related to infectious complications (recurrent angiocholitis) of severe Caroli's disease (dilatation of intra- and/or extra-hepatic bile ducts), a typical feature of ARPKD. Our data suggest that ARPKD patients evaluated for renal transplantation should be carefully screened for severe Caroli's disease. Even though the limited number of patients included in our study precludes any definite recommendation, pre-emptive liver transplantation may be a therapeutic option in ARPKD patients with severe Caroli's disease evaluated for renal transplantation.

Outpatient Renal Needle Biopsy of the Transplanted Kidney: Safety Profile

Since May 2005, we began performing renal graft biopsies as outpatient procedures when the patient's condition did not require hospitalization. To evaluate the safety profile of the 137 procedures performed in 111 patients, we performed a retrospective analysis of complications after all biopsies between 4 May 2005 and 6 January 6, 2011. The analysis focused on types of complications as well as needs for hospitalization with length of stay, for blood transfusion or for a further intervention. There were complications in 10.9% of procedures ( n = 15) with 8% requiring hospitalization ( n = 11). The complications were: gross hematuria ( n = 10) including blockage of urinary flow ( n = 2) with one subject requiring urologic intervention, and one patient experienced severe pain at the puncture site. Neither renal graft nor patient survival was threatened; there was no hemodynamic decompensation needing blood transfusions. The average hospital stay was 2.27 days (range = 1–8). Outpatient renal biopsies in 111 patients (137 procedures) had an 8% incidence of complications requiring admission and an average length of hospitalization of 2.27 days. Gross hematuria the most frequent problem, in no way compromised patient or graft survival showing it to be a safe outpatient procedure.

Enteric‐coated mycophenolate sodium in de novo and maintenance kidney–pancreas transplant recipients

Our objective was to describe efficacy and safety of enteric-coated mycophenolate sodium (EC-MPS) in de novo and maintenance recipients of kidney-pancreas transplant in the clinical practice. Observational, multicentre, prospective, 12-month study. We included 24 de novo and 24 maintenance patients. EC-MPS mean (± SD) doses at initiation in de novo patients were 1440 ± 0 vs. 1268 ± 263 mg/d at month 12 (M12). Patient and renal graft survival at one yr were 100%, and pancreatic graft survival was 83.3% (two losses owing to technical failure and two owing to rejection). In the maintenance cohort, EC-MPS was introduced at a median (P25-P75) of 30 (6-71) months after transplant. Baseline doses were 585 ± 310 vs. 704 ± 243 mg/d at M12. In this group, a significant increase in creatinine clearance was observed (65 ± 22 at baseline vs. 74 ± 20 mL/min at M12, p = 0.011). Patient, renal, and pancreatic graft survival were 100%, 95.8%, and 100%, respectively (one kidney graft loss owing to rejection). During follow-up, one patient from each group discontinued EC-MPS. The efficacy of EC-MPS in the clinical practice of kidney-pancreas transplantation is good, with high patient and grafts survival at 12 months, and good safety profile. The maintenance group displayed an improvement in renal function.

Clinical application of mTORi based immunosuppression for renal transplantation in India

Long-term renal graft survival is hampered by allograft dysfunction and cardiovascular disease resulting from calcineurin inhibitors (CNIs). This has led to the development of immunosuppressive regimens involving mammalian target of rapamaycin (mTOR) inhibitors, sirolimus and everolimus. They seem to provide long-term benefits for kidney function in transplant patients because of their anti-proliferation and anti-tumor properties and absence of nephrotoxicity. Their use has been evaluated in therapeutic regimens aimed at reducing the nephrotoxicity associated with CNIs. Both proactive and reactive strategies have been used. Whether existing strategies of using mTORi in renal transplantation is applicable for Indian patient's remains to be seen. Data on side effect profile, economic viability and the impact of these drugs on infections, particularly in India, are worth documenting. After briefly reviewing available data from India, this article explores the indications, patient populations; timing and practical aspects as well as the safety and efficacy of mTORi-based regimens for renal transplantation and suggests a framework which could allow transplant physicians to tailor its use to their own practice with particular reference to the Indian subcontinent.

Impact of Recurrent Glomerulonephritis on Renal Graft Survival

BackgroundGlomerular disease causes graft loss in the intermediate and long term, especially recurrent primary renal disease, negatively impacting graft survival. Thus, it must be considered a differential diagnosis in the evaluation of chronic graft dysfunction. MethodsThe objectives of our study were to compare the impacts of primary glomerular disease on graft survival and association with interstitial fibrosis/tubular atrophy (IFTA) or transplant glomerulopathy. We examined the influence of the relapse of glomerulonephritis (GN) on renal graft survival in a retrospective study of 1057 patients undergoing renal transplantations between March 1981 and October 2009. Among this group, 128 patients were diagnosed with pretransplant GN by renal biopsy. We examined graft survival on recurrence compared with IFTA and transplant glomerulopathy using Kaplan-Meier analysis. ResultsWe analyzed a cohort of 128 patients who were diagnosed with pretransplant GN by renal biopsy, including 28.9% (37) of whom were males. The mean age was 42.04 ± 13.82 years. The most frequent type was immunoglobulin A GN (IgAGN; 31.3%), followed by membranoproliferative GN (MPGN; 28.9%), rapidly progressive GN (RPGN; 16.4%), focal-segmental GN (FSGN; 13.3%), membranous GN (9.4%), and minimal change GN; (0.8%). Among the 16 cases (12.5%) of GN recurrence; MPGN was associated most frequently (n = 10, 28.9%), followed by FSGN (n = 4, 23.5%), RPGN (n = 1, 4.8%), and IgAGN (n = 1, 2.5%). We noted that 11.8% of subjects to be positive for hepatitis C virus; while 3.9% were hepatitis B virus(HBV)-positive. We observed no differences in hepatic serology between patients who experienced recurrence (HBV 6.3% vs hepatitis C virus [HCV] 18.8%) compared with IFTA (HBV 3.1% vs HCV 9.4%). Fifty-one patients (39.8%) were biopsied after transplantation due to impaired renal function: there were recurrences of GN in 12.5% (n = 16), IFTA in 25% (n = 32), and transplant glomerulopathy in 2.3% (n = 3) cases. The average graft survival in our cohort was 8.36 ± 0.59 years. The median patient survival among those who experienced a recurrence was 8.36 ± 1.79 years; 7.19 ± 1.01 years in IFTA patients; and 3.31 ± 0.91 years in patients with transplant glomerulopathy (log-rank P = .06). Upon multivariate analysis, recurrence of GN was not an independent predictor of renal loss. ConclusionsMPGN was the type of GN that recurred most frequently followed by FSGN. No differences in graft survival were noted between long-term recurrence of GN and other causes of chronic graft dysfunction. The recurrence of primary disease did not worsen the renal graft prognosis versus other causes of chronic graft dysfunction.

Impacto da função retardada do enxerto pancreático no transplante simultâneo pâncreas-rim

Simultaneous pancreas-kidney transplantation is an effective treatment for patients with type 1 diabetes mellitus and end-stage chronic kidney disease. Delayed pancreatic graft function is a common and multifactor condition with significant impact in short-term outcome of simultaneous pancreas-kidney transplantations. The aim of this study was to analyze the impact of pancreatic delayed pancreatic graft function on simultaneous pancreas-kidney transplantation. Donor and recipient's demographic data, percentage of panel reactivity, acute rejection incidence, and patient and grafts survivals were retrospectively analyzed in 180 SPKT performed between 2002 and 2007. The incidence of pancreatic delayed pancreatic graft function was 11%. Donors older than 45 years had significant risk of pancreatic delayed pancreatic graft function (OR 2.26; p < 0,05). Patients with pancreatic delayed pancreatic graft function had higher rates of acute renal rejection (47 versus 24%; p < 0.05), altered fasting plasma glucose (25 versus 5%; p < 0.05) and mean glycated hemoglobin (5.8 versus 5.4%; p < 0.05), than patients without pancreatic delayed pancreatic graft function at the end of the first year of follow up. There were no significant differences between patients with and without pancreatic delayed pancreatic graft function regarding patient survival (95 versus 88.7%; p = 0.38), pancreatic graft survival (90 versus 85.6%; p = 0.59) and renal graft survival (90 versus 87.2%; p = 0.70), respectively at the sample period of time. Pancreatic delayed pancreatic graft function had no significant impact in the short-term outcome of simultaneous pancreas-kidney transplantations. Although delayed pancreatic graft function had no impact on 1-year pancreas graft survival, it contributed to early pancreas graft dysfunction, as assessed by enhanced insulin and oral anti-diabetic drugs requirements.